Chromato-mass spectrometers GC-MS, is a combination of a gas chromatograph (GC), an electron impact ionization source (EI), and a mass spectrometer (MS). GC-MS are widely used for environmental, forensic, and clinical applications. Whenever analyte compounds are volatile enough, GC-MS is preferred over LC-MS, since it provides high-resolution and highly predictive chromatography, quantitative ionization, and NIST library identification.
GC-MS can be used in a number of applications, such as analyses as PCB and pesticides that require analyses in wide dynamic range over 6 or 7 orders of magnitude. The upper load into the GC column is limited to approximately 10 ng (1E-8 g) per compound both by the gas chromatography (at 1 mL/min helium flow) and by the linear response of EI sources. Thus, a desire for a large dynamic range translates into improving the detection limit (LOD) to a level around 1-10 fg (1E-15 g-1E-14 g) per trace compound of interest within complex matrices.
Most common GC-MS instruments employ quadrupole analyzers due to their low cost. Though these instruments employ so-called “closed” EI sources, which concentrate sample and improve ionization efficiency to approximately 1%, the LOD of quadrupolar GC-MS only reaches approximately 1 pg (1E-12 g), primarily due to mass scanning losses in the quadrupolar analyzers and to low resolution of the mass analyzer.
GC-TOF (such as the Pegasus GC-TOF by LECO Corp, Michigan, US) provides several analytical advantages over quadrupole GC-MS. A singly reflecting time-of-flight (TOF MS) analyzer provides rapid spectral acquisition and detects all ions in a full mass range without scanning losses. The analyzer has wide spatial acceptance, which is sufficient for unity ion transmission. Because of fast and non-skewed spectral acquisition, GC-TOF allows fast GC and better de-convolution of partially overlapping GC peaks, such as multi-dimensional GC (GC×GC) for enhanced separation of up to about 10,000 components.
While quadrupolar GC-MS employ so-called “closed” EI sources, generating a continuous ion beam, GC-TOF employ so-called “open” EI sources, accumulating ions within a potential well of an electron beam, which eliminates ion losses between pulses of the TOF analyzer. An “open” electron impact (EI) ion source has earned the reputation of a robust and never-cleaned EI source. GC-TOF provides strong ionic signals—up to 10,000 ions per pulse at 10 kHz frequency. However, the detection limit (LOD) has been comparable to quadrupole GC-MS (i.e. 1 pg).
Compared to “open” sources, the LOD of GC-TOF has been improved to about 100 fg with the introduction of semi-open EI ion sources (so-EI) per WO2013163530, which improves sample ionization efficiency and concentrates analyte molecules (but not the chemical background), while still preserving ion accumulation features. The LOD also improves to100 fg when using standard “open” EI source and dual stage GC×GC because of temporal sample concentration over the chemical background and matrix. Both observations indicate that LOD may be limited primarily by mass spectral interference with a complex matrix and chemical background (say, oil from pumping system). Then, one would expect better LOD when using instruments of higher specificity, either of higher resolution at single MS or of higher selectivity at tandem MS-MS.
Recently introduced GC-MR-TOF (such as “Citius GC-HRT” by LECO Corp) employs a closed EI source and high resolution multi-reflecting TOF (MR-TOF) analyzers with orthogonal accelerator (OA). In spite of high resolution (R=25-40K) the instrument also has comparable LOD=0.1-1 pg, most likely because of duty cycle losses in the OA at rare MR-TOF pulses.
Recently emerging GC-Q-TOF tandems (such as the GC-Q-TOF by Agilent) employ a “closed” EI source, quadrupole filter for selecting parent ions, CID cell for ion fragmentation, and singly reflecting TOF with an orthogonal accelerator for fragment analysis. In spite of improved specificity (MS-MS is expected to separate analyte signal from matrix and chemical background), GC-Q-TOF has demonstrated a LOD of only about 0.1 pg (i.e. a moderate improvement compared to previous GC-MS), presumably due to ion losses in transfer optics and duty cycle losses in the orthogonal accelerator.
Thus, existing GC-MS instrumentation have not improved LOD to a 1-10 fg level by using multiple means including: highly efficient “closed” EI sources; accumulating open and semi-open EI sources; non-scanning TOF analyzer with wide acceptance; high resolution MR-TOF instruments; and highly selective MS-MS instruments.
Thus, there still remains a practical problem of improving sensitivity at GC-MS analysis, preferably implemented in low complexity instruments while using robust and fast responding EI source and also having soft ionization features.